Genotype specific peripheral lipid profile changes with hepatitis C therapy

Abstract

AIMTo evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype.METHODSMono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol (TCHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component (direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene’s test and student’s t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3.RESULTSThree hundred and seventy five patients enrolled with 321 (85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1 (GT1), 18.1% genotype 2 (GT2), 9.7% genotype 3 (GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3 (ΔGT1, p and ΔGT3, p), with TCHOL increasing (+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing (+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing (+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing (-5.9, P = 0.044 and -9.80 P = 0.067). Among genotypes (ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL (+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL (+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2 (P = 0.028 and P = 0.019).CONCLUSIONSuccessful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.

Increase of Lipids During HCV Treatment: Virus Action or Medication?

“…More recently, studies show an increase of TC and LDL levels during treatment with DAAs (17,18) , as we observed. Meissner et al (16) , and Mark et al (19) , also observed a decrease in TG serum levels, as we observed as well.…”

“…Nevertheless, the DELTA TC and DELTA LDL were higher in genotype 3 patients, although DELTA triglycerides were lower in genotype 1. Mark et al (19) , observed which DELTA cholesterol levels were higher in GTP 3 than in GTP 1 and 2 (0.028 and 0.019 respectively).…”

“…On the other hand, other study reported a lipid increase in posttreatment (15) . Concerning DAAs, recent studies suggest that TC and LDL serum levels increase after the end of treatment, whereas triglyceride levels decrease (16,17,18,19) . However, the behavior of serum levels along with the sustained virologic response is not yet clear, that is, whether the relapse or the non-response to treatment could be accompanied by these lipidic alterations.…”

Cure or curd: Modification of lipid profiles and cardio‐cerebrovascular events after hepatitis C virus eradication

“…On the other hand, HCV eradication by interferon‐based therapy reverses hypolipidemia, 5 and this results should also be found after therapy with direct‐acting antivirals (DAAs) 6–8 . Nevertheless, the results have not been consistent regarding certain lipid profiles across studies 8–10 …”

Clinical effects of simvastatin in chronic hepatitis C patients receiving sofosbuvir/daclatasvir combination. A randomized, placebo-controlled, double-blinded study

“…HCV utilizes peripheral lipid metabolism pathways including hepatocyte very-low-density lipoprotein (VLDL) for viral assembly and requires several apolipoproteins for production of infective particles [3]. As a result, chronic hepatitis C (CHC) is associated with reduced total cholesterol, low-density lipoprotein (LDL) and apolipoprotein B (ApoB) levels as well as an increased rate of insulin resistance (IR) and type 2 diabetes mellitus [4].…”